Daratumumab has demonstrated good efficacy when used in combination with lenalidomide/dexamethasone and bortezomib/dexamethasone, respectively.1,2 To determine the ability of daratumumab to drive deep clinical responses beyond complete response (CR), minimal residual disease (MRD) was assessed in both the POLLUX and CASTOR clinical trials.
In both studies, MRD was assessed at the time of suspected CR and at 2 subsequent points in time. The MRD-negative rate per treatment arm was defined as the proportion of patients with negative MRD at any time point after the first dose. The addition of daratumumab resulted in significantly higher MRD-negative rates at all 3 thresholds examined (10-4, 10-5, and 10-6). Patients with sustained MRD negativity over time also showed significantly longer progression-free survival (PFS) with daratumumab-containing regimens.
These 2 groundbreaking studies represent the first randomized, controlled, prospective evaluation of MRD in the relapsed/refractory multiple myeloma phase 3 clinical trial setting. In the study, daratumumab-containing therapies consistently demonstrated greater MRD-negative rates compared with the control groups at all evaluated thresholds. Because MRD-negative patients treated with daratumumab had longer PFS than patients treated without daratumumab, the authors concluded that the deep clinical responses induced by daratumumab may also lead to improved survival.
Avet-Loiseau H, et al. ASH 2016. Abstract 246.
- Dimopoulos MA, et al. N Engl J Med. 2016; in press.
- Palumbo A, et al. N Engl J Med. 2016; in press.